The mechanism of mutagenesis will be studied by determining the relation of dose, measured as adducts per deoxynucleotides (APdN), to genetic effect. The genetic effect is measured by detecting mutations induced in germ cells of Drosophila melanogaster with an exposure to the non labeled alkylating agent equal to the dosimetry exposure. In this project both alkylation and the genetic consequence of alkylation are studied within the same germ cell stage in a eukaryote that can be throughly and economically analyzed genetically. We distinguish between dose, measured as APdN of DNA, and exposure of the whole organism, measured as concentration in the feeding solution or the amount injected. The importance of distinguishing between dose and exposure is illustrated in our work where we found a non-linear relation between exposure to EMS, concentration in the feeding media, and dose (ApdN); however, a linear relation was observed between dose and induced mutation frequency. For the dose-response curve no threshold was apparent and the statistical limit of the exponent was 1.0 (plus/minus) 0.1. The relation between APdN and mutations suggests that with EMS, EDB and EtO there is no change in mechanism of mutagenesis from low to high dose in Drosophila; however, MMS showed a significant departure from linearity. The genetic effect is determined with the sex-linked recessive lethal test (SLRL) and for mutations at the alcohol dehydrogenase locus (Adh) on the second chromosome. The SLRL test is an average of 600-800 loci. Mutations at the Adh locus can be studied in detail at the molecular level by comparing DNA of the mutant gene with DNA from a clone of this locus. These two genetic tests for mutations are complementary in that the SLRL test gives an average effect over a large sample of loci while mutations at the Adh locus can be analyzed in great detail at the molecular level. Dose and mutation frequency will be determined in sperm, spermatids, and oocytes. Molecular dosimetry of chemical mutagens permits us to distinguish between a non-linear relation of exposure to dose and a linear relation of dose to mutation induction.